DESCRIPTION (Investigator's Abstract): The focus of this proposal is on the earliest axon pathways that are formed in the brain, as small groups of well- defined neurons project axons to form specific and very reproducible tracts. Of particular interest is a longitudinal boundary which separates axons into separate longitudinal tracts. 1. The general mechanisms that guide the axons will be defined by a series of experimental surgeries in chick embryos, designed to distinguish between three possible classes of cues. 2. The trajectories of the early axons in chick and mouse will be compared to the expression patterns of adhesion molecules which have a potential role in axon guidance. 3. The function of the longitudinal boundary in axon guidance will be tested by altering its location by surgery (in chick embryos) or analysis of a genetic mutant (in mice). 4. The interactions of the axons with the boundary will be examined, both by describing the morphology of the leading growth cones, and by describing the cellular environment at the boundary. 5. A number of potential genetic regulatory genes have been previously reported, and here their expression pattern will be correlated with the axon patterns at the boundary. This work will be done on both the embryonic chicken, chosen because of its convenience, low price, and the potential for experimental surgery, and the embryonic mouse, chosen because of the wealth of genetic mutants, both natural and human-engineered, with defects shared by human diseases.